A Call for Systematic Research on Solute Carriers.

Solute carrier (SLC) membrane transport proteins control essential physiological functions, including nutrient uptake, ion transport, and waste removal. SLCs interact with several important drugs, and a quarter of the more than 400 SLC genes are associated with human diseases. Yet, compared to other gene families of similar stature, SLCs are relatively understudied. The time is right for a systematic attack on SLC structure, specificity, and function, taking into account kinship and expression, as well as the dependencies that arise from the common metabolic space.

Open drug discovery in Alzheimer's disease.

Alzheimer's disease (AD) drug discovery has focused on a set of highly studied therapeutic hypotheses, with limited success. The heterogeneous nature of AD processes suggests that a more diverse, systems-integrated strategy may identify new therapeutic hypotheses. Although many target hypotheses have arisen from systems-level modeling of human disease, in practice and for many reasons, it has proven challenging to translate them into drug discovery pipelines. First, many hypotheses implicate protein targets and/or biological mechanisms that are under-studied, meaning there is a paucity of evidence to inform experimental strategies as well as high-quality reagents to perform them. Second, systems-level targets are predicted to act in concert, requiring adaptations in how we characterize new drug targets. Here we posit that the development and open distribution of high-quality experimental reagents and informatic outputs-termed target enabling packages (TEPs)-will catalyze rapid evaluation of emerging systems-integrated targets in AD by enabling parallel, independent, and unencumbered research.

The burning island: Spatiotemporal patterns of fire occurrence in Madagascar.

Anthropogenic fire use is widespread across Madagascar and threatens the island's unprecedented endemic biodiversity. The vast majority (96%) of lemur species are already threatened with extinction, and Madagascar has already lost more than 44% of its forests. Previous conservation assessments have noted the role of fire in the rampant deforestation and habitat degradation across Madagascar, but published, quantified data on fire use across the island are incredibly limited. Here, we present the first quantification of spatiotemporal patterns in fire occurrence across Madagascar using VIIRS satellite fire detection data. We assess which regions of Madagascar have the most prevalent fire use, how fire use is changing over time, and what this means for Madagascar's remaining forest ecosystems. An average of 356,189 fires were detected every year in Madagascar from 2012-2019, averaging 0.604 fires/km2. Fire use was near-ubiquitous across the island, but was most prevalent in the western dry deciduous forests and succulent woodlands ecoregions. Fire frequency in the eastern lowlands was highest around the remaining humid rainforest, and fire frequency was increasing over time around much of the remaining humid and dry forest. We found that 18.6% of all remaining forest was within 500 m of a fire within a single year, and 39.3% was within 1 km. More than half of remaining forest was within 1 km of a fire in a single year in the dry deciduous forests, succulent woodlands, and mangroves ecoregions. However, fire frequency within national park protected areas was, on average, 65% lower than their surroundings. Only 7.1% of national park forest was within 500 m of a fire within one year, and 17.1% was within 1 km, suggesting that national parks are effective at reducing fire frequency in Madagascar's tropical forests.